Previous work in our laboratory has demonstrated that the coronary microcirculation is markedly impaired during the course of Trypanosoma cruzi infection. These observations have led us to consider that these early alterations lead to the focal pathology that attends chronic Chagasic cardiomypathy. Based on preliminary data concerning the interaction of T. cruzi infection- associated alterations in the mobilization of intracellular cAMP and Ca++ profoundly alter cellular function. This proposal examines the influence of T. cruzi infection on receptor complexes and related organelles involved in the generation and mobilization of cAMP and Ca++, respectively. With regard to the former, we shall examine the influence of parasite infection on the biochemical basis by which components of the adenylate cyclase complex i.e. receptors (R), guanine nucleotide binding proteins (Ns and Ni) and catalytic unit, interact in the generation of cAMP. In like manner, we shall investigate the influence of T. cruzi infection on Ca++ mobilization in endothelial host cells. Infection associated changes in the receptor populations involved in the mobilization of intracellular Ca++, and the generation of inositol phosphates will be examined. The possibility that infection alters storage of intracellular calcium will be explored. These studies will help characterize the influence of T. cruzi infection on biochemical systems known to regulate cell function, and may suggest potential therapeutic strategies for the treatment of this as yet incurable disease.